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Title: A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development.
Austin Authors: Eising, Else;Carrion-Castillo, Amaia;Vino, Arianna;Strand, Edythe A;Jakielski, Kathy J;Scerri, Thomas S;Hildebrand, Michael S ;Webster, Richard;Ma, Alan;Mazoyer, Bernard;Francks, Clyde;Bahlo, Melanie;Scheffer, Ingrid E ;Morgan, Angela T;Shriberg, Lawrence D;Fisher, Simon E
Affiliation: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, 6525 XD, The Netherlands
Department of Neurology, Mayo Clinic, Rochester, MN, 55905, USA
Department of Communication Sciences and Disorders, Augustana College, Rock Island, IL, 61201, USA
Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, 3052, Australia
Department of Medical Biology, University of Melbourne, Melbourne, 3010, Australia
Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, 3010, Australia
Department of Neurology and Neurosurgery, Children's Hospital Westmead, Sydney, NSW, Australia
Department of Clinical Genetics, Children's Hospital Westmead, Sydney, NSW, Australia
University of Bordeaux, IMN, UMR 5293, Bordeaux, France
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, 6500 HE, The Netherlands
Austin Health, Heidelberg, Victoria, Australia
Royal Children's Hospital, Melbourne, 3052, Australia
Neuroscience of Speech, Murdoch Childrens Research Institute, Melbourne, 3052, Australia
Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA
Issue Date: 2019
Date: 2018-02-20
Publication information: Molecular psychiatry 2019; 24(7): 1065-1078
Abstract: Genetic investigations of people with impaired development of spoken language provide windows into key aspects of human biology. Over 15 years after FOXP2 was identified, most speech and language impairments remain unexplained at the molecular level. We sequenced whole genomes of nineteen unrelated individuals diagnosed with childhood apraxia of speech, a rare disorder enriched for causative mutations of large effect. Where DNA was available from unaffected parents, we discovered de novo mutations, implicating genes, including CHD3, SETD1A and WDR5. In other probands, we identified novel loss-of-function variants affecting KAT6A, SETBP1, ZFHX4, TNRC6B and MKL2, regulatory genes with links to neurodevelopment. Several of the new candidates interact with each other or with known speech-related genes. Moreover, they show significant clustering within a single co-expression module of genes highly expressed during early human brain development. This study highlights gene regulatory pathways in the developing brain that may contribute to acquisition of proficient speech.
DOI: 10.1038/s41380-018-0020-x
ORCID: 0000-0001-9819-1260
Journal: Molecular psychiatry
PubMed URL: 29463886
Type: Journal Article
Appears in Collections:Journal articles

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